Biology

Prof. M. K. Mathew
NCBS, Bangalore

The beating of the heart is initiated by an elaborate and well tuned electrical system that generates the cardiac action potential. The firing of the Action Potential results in contractions of the musculature of the heart and hence blood flow through the body. The effect of mechanical forces at work during the heart beat on the electrical system of the heart have not, surprisingly, been investigated in detail so far. The fast component of the delayed rectifier potassium currents responsible for repolarization of the cardiac action potential, Ikr, is encoded by the hERG channel. When HEK293T cells expressing hERG1a channels were exposed to laminar shear stress, there was a substantial increase in whole cell current. hERG1b, which lacks the PAS domain, and long QT mutants containing point mutations in the PAS domain were unaffected by shear suggesting possible involvement of the PAS domain in mechanosensation. Modulation of the whole cell current upon application of shear was found to be dependent on the integrin pathway. Thus mechano-electric feedback modulates the hERG channel through the integrin pathway, thereby influencing the repolarization current in the heart.